Abstract

AimDuring exercise in humans, circulating levels of ATP and K+ increase at a time when blood flow increases to satisfy metabolic demand. Both molecules can activate arteriolar K+ channels to stimulate vasodilatation; here, it is established whether conducted dilatation is observed in a skeletal muscle bed.MethodsIsolated and cannulated rat cremaster arterioles were used to assess both local and conducted responses. Agents were either added to the bath, focally pulse‐ejected to the downstream end of arterioles, or in triple‐cannulated arterioles, luminally perfused into the downstream branches to assess both local and conducted responses.ResultsThe endothelium‐dependent agonist ACh and the KATP channel opener levcromakalim each stimulated both local and conducted vasodilatation. Focal, bolus delivery of ATP (10 μ m) or KCl (33 mm) to the outside of arterioles stimulated a biphasic vasomotor response: rapid vasoconstriction followed by dilatation as each washed away. At lower concentrations of KCl (19 mm), constriction was avoided, and instead, Ba2+‐sensitive local dilatation and conducted dilatation were both observed. Luminal perfusion of ATP avoided constriction and activated P2Y1 receptors stimulating vasodilatation secondary to opening of KC a channels. In triple‐cannulated arterioles, either ATP (10 μ m) or K+ (15 mm) luminally perfused into daughter branches of a bifurcation stimulated local dilatation which conducted into the parent arteriole.ConclusionThe recognized physiological autocrine and paracrine mediators ATP and K+ each act to evoke both local and conducted vasodilatation in rat cremaster arterioles. Therefore, in situations when circulating levels are raised, such as during exercise, these agents can act as important regulators of blood flow.

Highlights

  • The control of skeletal muscle blood flow is regulated by the extent of tone generated by intraluminal pressure and vasoconstrictors, balanced by the release of vasodilators from cells both within the artery wall and surrounding tissue (Clifford & Hellsten 2004, Clifford 2007)

  • KCa channels underlie the majority of the dilatation to ATP, while KIR channels are responsible for dilatation to modest increases in KCl concentration

  • Both mediators are generated during skeletal muscle contraction, and their ability to stimulate conducted dilatation will serve to reduce arteriolar resistance and improve blood flow into regions of ischaemia

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Summary

Introduction

The control of skeletal muscle blood flow is regulated by the extent of tone generated by intraluminal pressure (causing myogenic tone) and vasoconstrictors, balanced by the release of vasodilators from cells both within the artery wall and surrounding tissue (Clifford & Hellsten 2004, Clifford 2007). The use of the cremaster preparation for intravital studies in vivo clearly demonstrates that either reducing the PO2 across the tissue or electrical stimulation of skeletal muscle bundles can each stimulate vasodilatation of arterioles (Klitzman et al 1982, Hester & Duling 1988, Segal & Duling 1989, Cohen et al 2000, Cohen & Sarelius 2002). The vasodilator mediators responsible are not fully elucidated, but candidates include (i) ACh released from motor nerve endplates (Welsh & Segal 1997); (ii) ATP released from hypoxic erythrocyte

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